Ex Parte Nakagawa et al

Patent Trials and Appeals Board

May 23, 2019

13136801 - (D) (P.T.A.B. May. 23, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/136,801 08/11/2011
66981 7590 05/24/2019
HUGH MCTA VISH
MCT A VISH PA TENT FIRM
7460 Pinehurst Road
Pine Springs, MN 55115
FIRST NAMED INVENTOR
Mayumi Nakagawa
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
l 10.0038US2 8650
EXAMINER
DEBERRY, REGINA M
ART UNIT PAPER NUMBER
1647
MAIL DATE DELIVERY MODE
05/24/2019 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MA YUMI NAKAGAWA,
KEVIN KIM, and THOMAS HORN 1
Appeal2017-008721
Application 13/136,801
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
ULRIKE W. JENKS, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to pharmaceutical compositions
comprising a human papillomavirus polypeptide and a microorganism
antigen not found in human papilloma virus. The Examiner rejected the
claims under 35 U.S.C. § 112 for lack of written description and 35 U.S.C.
§ 103 as obvious. Pursuant to 35 U.S.C. § 134, Appellants appeal the
Examiner's determination that the claims are unpatentable. We have
jurisdiction for the appeal under 35 U.S.C. § 6(b). The Examiner's decision
is affirmed.
1 The Appeal Brief ("Br." entered Nov. 11, 2016) lists The Board of
Trustees of the University of Arkansas as the Real-Party-in-Interest. Br. 3.
Appeal2017-008721
Application 13/136,801
STATEMENT OF THE CASE
"Warts are benign epidermal tumors caused by human
papillomaviruses (HPV)." Spec. 1. The Specification describes the
administration of (a) antigens that induce a cutaneous delayed-type
hypersensitivity response and (b) L 1 and E4 HPV polypeptides to treat warts
and skin lesions in patients having HPV-induced warts. Spec. 2-3.
The claims stand rejected by the Examiner as follows:
1. Claim 35 under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA),
first paragraph, as failing to comply with the written description
requirement. Ans. 2.
2. Claims 16, 17, 26, and 30-35 under pre-AIA 35 U.S.C. § I03(a) as
obvious in view of Senger et al. (US 2012/0115207 Al; published May 10,
2012, priority date Mar. 30, 2010) ("Senger") and Sette et al. (US
2007 /0053922; published Mar. 8, 2007) ("Sette"). Ans. 2.
3. Claim 27 under pre-AIA 35 U.S.C. § I03(a) as obvious in view of
Senger, Sette, and Hirsch-Behnam et al. (Virus Research 18:81-98; 1990)
("Hirsch-Behnam"). Ans. 2.
4. Claims 28 and 37 under pre-AIA 35 U.S.C. § I03(a) as obvious in
view of Senger, Sette, and Hom et al. (US 2005/0175634 Al; published
Aug. 11, 2005) ("Hom"). Ans. 2-3.
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Application 13/136,801
Independent claim 16 is illustrative of the claimed subject matter and
reproduced below (indenting added for clarity):
16. A pharmaceutical composition comprising:
(a) a microorganism antigen not found in human
papilloma virus and capable of inducing a cutaneous delayed
type hypersensitivity response in a human when injected
intradermally; and
(b) (i) a polypeptide comprising human papillomavirus
(HPV) L 1 (SEQ ID NO: 1) or an antigenic fragment of SEQ ID
N0:1 comprising LI 380-412 (SEQ ID N0:3) or
(b) (ii) a polypeptide comprising HPV E4 (SEQ ID
N0:2) or an antigenic fragment of SEQ ID N0:2 comprising
E4 10-30 (SEQ ID N0:4); wherein the composition is capable
of treating a benign epithelial tumor caused by a human
papilloma virus.
Br. 13 (Claims Appendix).
1. WRITTEN DESCRIPTION REJECTION
Claim 3 5 depends from claim 16 and further recites, inter alia, "(b)
(ii) an antigenic fragment of 33-50 residues of SEQ ID N0:2 comprising E4
10-30 (SEQ ID N0:4)." The Examiner rejected claim 35 as lacking a
written description because the Examiner found that the claim does not
provide written description support for the lower limit of 33. Final Act. 4
To satisfy the written description requirement, the inventor must
"convey with reasonable clarity to those skilled in the art that, as of the filing
date sought, he or she was in possession of the invention." Vas-Cath, Inc. v.
Mahurkar, 935 F.2d 1555, 1563---64 (Fed. Cir. 1991). In describing the
claimed invention, there is no requirement that the wording be identical to
that used in the specification as long as there is sufficient disclosure to show
one of skill in the art that the inventor "invented what is claimed." Union
Oil Co. v. Atlantic Riclifield Co., 208 F.3d 989, 997 (Fed. Cir. 2000).
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Application 13/136,801
The Specification does not expressly disclose that the E4 fragment can
be 33 amino acid residues, but that value falls with the size ranges disclosed
in the Specification. The Specification discloses:
In particular embodiments, the polypeptide comprising
an antigenic fragment of L 1 or E4 is a polypeptide of 8-100
amino acid residues, 8-80, 8-60, 8-50, amino acid residues, 8, 9,
or 10 amino acid residues. In specific embodiment, the
polypeptide is a polypeptide of no more than 100, no more than
80, no more than 60, no more than 50, no more than 40, or no
more than 3 0 amino acid residues. In specific embodiments, it
is a polypeptide of at least 8, at least 9, at least 10, at least 12, at
least 15, at least 20, or at least 25 amino acid residues.
Spec. 6.
The disclosure of peptide size ranges that include 33 amino acid
residues ("8-80, 8-60, 8-50"), as well as specific embodiments of "no more
than 50, no more than 40" and "at least 25 amino acid residues," is sufficient
to satisfy the written description requirement. As held in In re Wertheim,
541 F.2d 257, 264--265 (CCPA 1976):
In the context of this invention, in light of the description
of the invention as employing solids contents within the range
of 25-60% along with specific embodiments of 36% and 50%,
we are of the opinion that, as a factual matter, persons skilled in
the art would consider processes employing a 35-60% solids
content range to be part of appellants' invention.
Accordingly, the written description rejection of claim 35 is reversed.
OBVIOUSNESS BASED ON SENGER AND SETTE (REJECTIONS 2--4)
The Examiner found that Senger describes manufacturing HPV
particles that correspond to a polypeptide sequence that is 100% identical to
SEQ ID NOS: 1 and 3 as required by (b )(i) of claims 16 and 35. Final
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Application 13/136,801
Act. 7. The Examiner also found that Senger describes a size range of
peptide fragments that meets the size limitations of claim 35. Id. The
Examiner found that Senger teaches that the composition is useful for the
treatment or prevention of HPV related diseases. Id. 8.
The Examiner acknowledged that Senger does not disclose that its
composition for preventing or treated HPV related diseases comprises "(a) a
microorganism antigen not found in human papilloma virus and capable of
inducing a cutaneous delayed type hypersensitivity response in a human
when injected intradermally" as recited in claim 16. However, the Examiner
found that Sette discloses peptides of HPV to induce an immune response to
HPV as does Senger. Final Act. 8. The Examiner found that Sette discloses
"employing an antigen not found in HPV, which is capable of inducing a
cutaneous delayed type hypersensitivity response in a human when injected
intradermally and is a microorganism antigen such as tetanus toxoid (paras
0170, 0174 and 0175)," meeting the limitation of (a) of claim 16. Final Act.
9. The Examiner concluded it would have been obvious to one of ordinary
skill in the art to have included tetanus toxoid in Senger's composition to
enhance the immune response in individuals, thereby meeting the claim
limitation. Id. at 10.
Appellants contend that neither Sette nor Senger disclose that
"inducing a cutaneous delayed-type hypersensitivity response enhances the
immune response to the HPV peptides" or "that tetanus toxoid is capable of
inducing a delayed-type hypersensitivity response when injected
intradermally." Br. 9.
This argument does not persuade us that the Examiner erred. Sette
teaches that tetanus toxoid can be used as a carrier (Sette ,r 174) in a
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composition comprising HPV peptides for the use of prevention or treatment
of HPV infection (Sette ,r,r 14, 18, 26). Sette also teaches that peptides from
tetanus toxoid can be used to enhance the immune response (Sette
,r,r 208, 210). In addition, as found by the Examiner, one of ordinary skill in
the art knew that tetanus toxoid "causes a delayed-type hypersensitivity
when injected intradermally and has been employed by scientists for years."
Ans. 9. As evidence of this, the Examiner cited two publications, Beeton2
and Hom, as disclosing that tetanus toxin can be used in to induce delayed
type hypersensitivity ("DTH") as required by the claims. Final Act. 15.
Hom is also cited in Rejection 4. Hom specifically teaches in paragraphs 37
and 40 that tetanus induce DTH:
[0037] In particular embodiments, the subject is a human. In
particular embodiments, the antigen is an antigen to which the
human has a preexisting sensitivity such that the antigen
induces a cutaneous delayed type hypersensitivity response in
the human subject.
[0040] In other particular embodiments, the antigen is a
trichophyton, candida, blastomyces, histoplasma, mumps,
measles, rubella, polio, diphtheria, tetanus, pertusis,
staphylococcus, or streptococcus antigen.
A preponderance of the evidence thus supports the Examiner's
findings that tetanus toxoid was known at the time of the invention to induce
cutaneous delayed type hypersensitivity as required by the claims.
Appellants' argument to the contrary is not supported by the evidence in the
record before us.
2 Beeton, C. et al. Induction and monitoring of active delayed type
hypersensitivity (DTH) in rats. Journal of visualized experiments: Jo VE,
ABSTRACT. No. 6, pages 237 (July 19, 2007).
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Appellants contend that the "aggregation of LI protein is already
taught to enhance its imnmnogenicity. So there would be less or no need for
other factors that might enhance its immunogenicity. And Sette does not
teach that tetanus toxoid enhances immunogenicity anyway." Br. 9.
We do not agree. First, Sette expressly teaches that tetanus toxoid can
be used in HPV vaccine composition as a carrier (Sette ,r 174), and when
included as such, the tetanus toxoid would inherently induce DTH. As
explained by the Examiner (Ans. 10-11): "[T]he discovery of a previously
unappreciated property of a prior art composition, or of a scientific
explanation for the prior art's functioning, does not render the old
composition patentably new to the discoverer." Atlas Powder Co. v. Ireco
Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999). Thus, claiming a new use, new
function, or unknown property that is inherently present in the prior art does
not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254
(CCPA 1977). Ans. 11.
Second, as discussed above, Sette discloses tetanus peptides enhance
the immune response. Sette ,r 208 ("For instance, the ability of a peptide to
induce CTL activity can be enhanced by linking the peptide to a sequence
which contains at least one epitope that is capable of inducing a T helper cell
response."); id. ,r 210 ("In certain embodiments, the T helper peptide is one
that is recognized by T helper cells present in the majority of the population.
. . . Examples of amino acid sequences that are promiscuous include
sequences from antigens such as tetanus toxoid at positions 830-843.")
Appellants also argue there is "no motivation at all" to combine HPV
with tetanus toxoid. Br. 9-10. We do not agree. As discussed by the
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Examiner, the reason for combining references does not have to be the same
reason supplied by the inventors. Final Act. 17.
In determining whether the subject matter of a patent claim is obvious,
neither the particular motivation nor the avowed purpose of the
patentee controls. . . . [ A ]ny need or problem known in the field of
endeavor at the time of invention and addressed by the patent can
provide a reason for combining the elements in the manner claimed."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 419-20 (2007).
In this case, the reason to combine Senger' s HPV peptides with
tetanus toxin is Sette' s teaching that tetanus can be used as carrier in a
vaccine composition comprising HPV peptides (Sette ,r 174) and,
independently, Sette's teaching that tetanus can be used to enhance the
immune response (id. ,r,r 208, 210).
Appellants also argue that "Senger does not disclose intradermal
injection, and Sette, although it does disclose intradermal injection, does not
suggest it is more favorable than any other route of injection and does not
link tetanus toxoid with intradermal injection." Br. 9.
We do not agree. Sette expressly teaches the intradermal route. Sette
,r 229. The intradermal injection route does not have to be the most
favorable route to have been obvious to one of ordinary skill in the art. A
teaching that a process would be inferior or less desirable is not a teaching
away unless the use would render the process "inoperable." See In re ICON
Health and Fitness Inc., 496 F.3d 1374, 1381 (Fed. Cir. 2007); In re Gurley,
27 F.3d 551, 553 (Fed. Cir. 1994). "[J]ust because better alternatives exist
in the prior art does not mean that an inferior combination is inapt for
obviousness purposes." In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir.
2012).
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For the foregoing reasons and those of the Examiner, the rejection of
claims 16 and 26 is affirmed. Claims 17 and 30-35 were not argued
separately and fall with claims 16 and 26. 37 C.F.R. § 4I.37(c)(l)(iv).
Claim 27
Claim 27 depends from claim 16, and further recites "wherein the
polypeptide comprises SEQ ID N0:4." SEQ ID N0:4 is (b )(ii) of claim 16
and "an antigenic fragment of SEQ ID N0:2 [HPV E4] comprising E4 10-30
(SEQ ID N0:4)." The Examiner found Hirsch-Behnam discloses an HPV
antigen of polypeptide sequence 100% identical to SEQ ID NOS:4 and 2.
Final Act. 10. The Examiner found it would have been obvious to one of
ordinary skill in to have included the polypeptide in Senger because Senger
teaches that "it would be desirable to include more HPV types in vaccine
formulations in order to extend protection to rarer, but nonetheless high risk
HPV types" and to treat HPV. Final Act. 11.
Appellants contend that Hirsch-Behnam "does not even disclose a
sequence 100% identical to the LI protein SEQ ID N0:2. It does not
disclose the present SEQ ID N0:4 as a peptide fragment of interest of L 1, or
any peptide fragments of L 1." Br. 10. This argument has no merit. Claims
16 comprises (b )(i) which is HPV L 1 or (b )(ii) which is HPV E4. The
Examiner cited Hirsch-Behnam for teaching (b )(ii) HPV E4. Appellants'
argument regarding the publication's lack of disclosure of LI therefore has
no merit because Senger was cited for this disclosure, not Hirsch-Behnam.
See Ans. 14--15.
For the foregoing reasons and those of the Examiner, the rejection of
claims 16 and 26 is affirmed.
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Claims 28 and 37
Claim 28 depends from claim 16 and further recites "wherein the
composition comprises candida antigen, trichophyton antigen, or mumps
antigen." Claim 37 depends from claim 26 and further recites "wherein the
antigen capable of inducing a cutaneous delayed type hypersensitivity
response in a human when injected intradermally comprises candida antigen,
trichophyton antigen, or mumps antigen." In each case, the antigens
correspond to component (a) of the claims. The Examiner acknowledged
that neither Senger or Sette describe these antigens, but relied upon the
disclosure in Hom of treating humans having HPV epithelial induced tumors
by administering candida and mumps antigen intradermally which induce a
cutaneous delayed type hypersensitivity response in the subject. Final Act.
12-13. The Examiner determined it would have been obvious to one of
ordinary skill in the art to have utilized candida or mumps in Senger's
composition to treat HPV as described in both Senger and Hom. Id. at 14.
Appellants argue that Hom does not disclose or suggest "combining
killed mumps virus, candida extract, or Trichophyton extract, or any other
antigen that induces a delayed-type hypersensitivity response, with any HPV
peptides or polypeptides in a pharmaceutical composition, as recited in
claims 28 and 37." Br. 11. Appellants contend that the Examiner's
reasoning is "conclusory," and that the Examiner "does not cite where in the
prior art the motivation to include HPV peptides in the composition of Hom
found." Id. at 12.
The Examiner thoroughly responded to this argument, which we
incorporate herein. Ans. 17. We additionally note that Senger teaches that
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its peptides are useful to HPV (Senger ,r,r 24, 30, 34) and that Hom teaches
that the DTH peptides candida and mumps can be injected intradermally to
treat an HPV associated tumor (Hom ,r,r 17, 18, 25). Both compositions are
therefore described as useful to treat HPV. As stated in KSR, 550 U.S. at
417,
[I]f a technique has been used to improve one device, and
a person of ordinary skill in the art would recognize that it
would improve similar devices in the same way, using the
technique is obvious unless its actual application is beyond his
or her skill. ... [A] court must ask whether the improvement is
more than the predictable use of prior art elements according to
their established functions.
Each of the HPV peptide and candida and mumps are being used for their
"established functions" in treating HPV. ("It is prima facie obvious to
combine two compositions each of which is taught by the prior art to be
useful for the same purpose, in order to form a third composition to be used
for the very same purpose. . . [T]he idea of combining them flows logically
from their having been individually taught in the prior art." In re
Kerkhoven, 626 F.2d 846, 850 (CCPA 1980) (citations omitted).).
For the foregoing reasons and those of the Examiner, the rejection of
claims 16 and 26 is affirmed.
Claims 34
Claim 34 depends from independent claim 16 and dependent claim
17, and further recites "wherein the polypeptide is amidated at its C-
terminus." The Examiner found that Sette discloses peptide amidation as
recited in the claim. Final Act. 9. The Examiner stated the skilled worker
would have been motivated to use amidation because it is "known to provide
sites for linking to other molecules, which would be useful if the
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pharmaceutical further comprised a cytokine or colony stimulating factor, as
taught by Sette." Id. 9-10.
Appellants argue that Senger does not disclose amidation. Br. 8. This
argument is unavailing as the Examiner relied on Sette for this disclosure.
For the foregoing reasons and those of the Examiner, the rejection of
claim 34 is affirmed.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv).
AFFIRMED
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